: Studies in this grant period will focus on the hypothesis that chronic hypersecretion of LH, with a significant contribution from FSH, causes tumor formation by altering expression of a complex network of genes including a progressive down-regulation of the LH receptors and an increase in cyclin D2. The investigators will also map and clone the three non-allelic variants in the CF-1 genome necessary for GC tumorigenesis and contribute to its complete penetrance. In identifying gene expression profiles unique to the formation of granulosa cell tumors, these studies should contribute to a better understanding of permissive and causative events that underlie tumor formation.